Article: Nicotinamide Riboside Enhances NK Cell Anti-Tumor Activity: Preclinical Findings

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Cancer Immune Health Preclinical

Nicotinamide Riboside Enhances NK Cell Anti-Tumor Activity: Preclinical Findings

Synopsis

Tumor-produced lactate weakens natural killer (NK) cells by causing lysine lactylation (Kla), disrupting NAD+ metabolism, and fragmenting mitochondria, which reduces cytotoxicity. Supplementing with nicotinamide riboside (NR), an NAD+ precursor, and honokiol, a SIRT3 activator, lowered Kla levels, restored mitochondrial health, and enhanced NK cell cancer-killing activity. This combination reactivated antileukemic NK cell function by modulating ROCK1–DRP1 signaling, preventing mitochondrial fragmentation. These findings suggest targeting lactylation with NR and SIRT3 activation strengthens NK cell–based immunotherapy in cancer.

Journal

Nature Immunology

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